This Award will allow the candidate to have the protected time necessary to focus on new and emerging MRI-based research projects in MS and provide an opportunity to become well-grounded in new areas of study relevant to his research field. Under the guidance of his mentor, co-mentor and Research Advisory Committee, the candidate will develop independent research skills and abilities in longitudinal clinical investigations and advanced magnetic resonance techniques, including diffusion tensor imaging. This mentored training experience will lead to his establishment as an independent, patient-oriented translational investigator in the following years. Multiple Sclerosis (MS) is an inflammatory disorder of the central nervous system which leads to tissue destruction and brain atrophy. Magnetic resonance (MRI) technology allows direct visualization of ongoing disease processes and has been useful in following patients over time and evaluating therapeutic interventions. We will apply advanced magnetic resonance techniques to multiple sclerosis patients in longitudinal clinical studies in order to better understand MS pathogenesis and the effects of therapeutic interventions. Aim 1 will evaluate if the short-term changes in measures of brain atrophy induced by corticosteroid infusions correlate with the subsequent rate of disease progression. We hypothesize that the short-term decline in brain parenchymal fraction (BPF) following intravenous methylprednisolone predicts increased subsequent disease progression. In Aim 2 we will describe the diffusion tensor characteristics of multiple sclerosis brain lesions recovering from acute inflammation. This project will lead to greater insights into sensitive monitoring strategies of the pathologic process of brain tissue injury during the course of MS. These insights should lead to methods to provide for more accurate advice to MS patients in the early stages of disease, for better therapeutic decision making, and for monitoring therapeutic responses in individual MS patients. Furthermore, these studies should help develop improved methods for evaluating new therapeutic strategies for neuroprotection and neuroregeneration.